Macrophage Migration Inhibitor (MIF) Therapeutics for Neuroprotection and Prevention of Scar in Traumatic Retinal Detachment
Abstract
Retinal detachment (RD) is one of the gravest military-relevant injuries to the visual system caused by ocular trauma. Severe vision loss and blindness result from the death and degeneration of the photoreceptors as well as from excessive retinal scar formation, a disorder known as proliferative vitreoretinopathy (PVR), which occurs at elevated rates following ocular trauma. Blast injury is also a common component of battlefield trauma and a major molecular mechanism is excitotoxic damage with N-Methyl-D-aspartic acid (NMDA) receptor activation. There is currently inadequate mitigation and treatment of these types of retinal damage following ocular trauma. Inflammation plays a critical role in these vision threatening processes following RD. This proposal stems from our recently published work which identified macrophage migration inhibitory factor (MIF) as a key player in retinal injury associated with RD and unpublished work on NMDA mediated retinal damage. MIF is a pro-inflammatory cytokine with a key role in innate and acquired immune responses. In the murine RD model, systemic administration of the MIF inhibitor ISO-1 significantly blocked photoreceptor apoptosis, outer nuclear layer thinning, and retinal gliosis. Our work on a chick model, which has a cone-rich retina and similar damage responses to humans following RD, demonstrates that MIF is upregulated following NMDA-induced excitotoxicity. This elevation in MIF levels is associated with increases in cell apoptosis in the chick retina. Administration of intravitreal ISO-1 protected the retina from the NMDA-induced damage. These pre-clinical data have clinical relevance; elevated MIF levels have been detected in the vitreous and subretinal fluid of patients with RD developing PVR compared with those without PVR(13, 14), providing a rationale for future clinical therapy in high-risk RDs.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2024
- Accession Number
- AD1228219
Entities
People
- Colleen M. Cebulla
- Diana Summitt
- Elizabeth Urbanki
- Kayla Bernstein
- Sumaya Hamadmad
- Tyler Heisler-Taylor
Organizations
- Ohio State University